Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.

Flash glucose monitoring with the FreeStyle Libre 2 compared with self-monitoring of blood glucose in suboptimally controlled type 1 diabetes: the FLASH-UK randomised controlled trial protocol.

INTRODUCTION: Optimising glycaemic control in type 1 diabetes (T1D) remains challenging. Flash glucose monitoring with FreeStyle Libre 2 (FSL2) is a novel alternative to the current standard of care self-monitoring of blood glucose (SMBG). No randomised controlled trials to date have explored the potential benefits of FSL2 in T1D. We aim to assess the impact of FSL2 in people with suboptimal glycaemic control T1D in comparison with SMBG. METHODS: This open-label, multicentre, randomised (via stochastic minimisation), parallel design study conducted at eight UK secondary and primary care centres will aim to recruit 180 people age ≥16 years with T1D for >1 year and glycated haemoglobin (HbA1c) 7.5%-11%. Eligible participants will be randomised to 24 weeks of FSL2 (intervention) or SMBG (control) periods, after 2-week of blinded sensor wear. Participants will be assessed virtually or in-person owing to the COVID-19 pandemic. HbA1c will be measured at baseline, 12 and 24 weeks (primary outcome). Participants will be contacted at 4 and 12 weeks for glucose optimisation. Control participants will wear a blinded sensor during the last 2 weeks. Psychosocial outcomes will be measured at baseline and 24 weeks. Secondary outcomes include sensor-based metrics, insulin doses, adverse events and self-report psychosocial measures. Utility, acceptability, expectations and experience of using FSL2 will be explored. Data on health service resource utilisation will be collected. ANALYSIS: Efficacy analyses will follow intention-to-treat principle. Outcomes will be analysed using analysis of covariance, adjusted for the baseline value of the corresponding outcome, minimisation factors and other known prognostic factors. Both within-trial and life-time economic evaluations, informed by modelling from the perspective of the National Health Service setting, will be performed. ETHICS: The study was approved by Greater Manchester West Research Ethics Committee (reference 19/NW/0081). Informed consent will be sought from all participants. TRIAL REGISTRATION NUMBER: NCT03815006. PROTOCOL VERSION: 4.0 dated 29 June 2020.

Genetic diversity and population structure of Culex modestus across Europe: does recent appearance in the United Kingdom reveal a tendency for geographical spread?

In mainland Europe, the mosquito species Culex modestus Ficalbi (1890) is a bridge vector for West Nile virus (WNV) from its natural bird-mosquito cycle to mammals. The present study assessed the genetic diversity of Cx. modestus, as well as related Culex species, using the mitochondrial COI DNA barcoding region and compared this with the population structure across Europe. A haplotype network was mapped to determine genealogical relationships among specimens. The intraspecific genetic diversity within individual Culex species was below 2%, whereas the interspecific genetic divergence varied from 2.99% to 13.74%. In total, 76 haplotypes were identified among 198 sequences. A median-joining network determined from 198 COI sequences identified two major lineages that were separated by at least four mutation steps. A high level of intraspecific genetic diversity was not detected in Cx. modestus in samples submitted from different European populations, which indicates that morphologically identified specimens represent a single species and not a species complex. Therefore, it is deduced that different populations of Cx. modestus will show a similar potential to transmit WNV, lending support to concerns that the population present in southeast England represents a risk of transmission to humans.

Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak.

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.

Non-fatal case of Crimean-Congo haemorrhagic fever imported into the United Kingdom (ex Bulgaria), June 2014.

Crimean-Congo haemorrhagic fever (CCHF) was diagnosed in a United Kingdom traveller who returned from Bulgaria in June 2014. The patient developed a moderately severe disease including fever, headaches and petechial rash. CCHF was diagnosed following identification of CCHF virus (CCHFV) RNA in a serum sample taken five days after symptom onset. Sequence analysis of the CCHFV genome showed that the virus clusters within the Europe 1 clade, which includes viruses from eastern Europe.

The combination of specific IgM antibodies and IgG antibodies of low avidity does not always indicate primary infection with cytomegalovirus.

The detection of CMV specific IgM antibodies coupled with IgG antibodies of low avidity is taken as diagnostic of primary CMV infection. In a study of 64 pregnant women referred for avidity testing, six women were identified with bloods with positive IgM and low/equivocal avidity IgG on the Abbott Architect assay persisting over 18 weeks. Avidity increased to an "equivocal" level in two women over the course of follow up but remained "low" in four women. On repeat testing with the Diasorin Liaison assay, bloods from two women with low avidity with Architect gave high avidity results with Liaison. Blood from one woman giving low/equivocal results with Architect was reported as moderate avidity on repeat with Liaison. There is concern from these small numbers of cases that some women with positive IgM and low avidity IgG using the Abbott Architect assay may not have primary infections. This implies that they could be entered inappropriately into trials of experimental treatments aiming to prevent transmission of CMV to the fetus if the laboratory is asked to test patients for this purpose. It is suggested that larger series of patients should be examined to determine how frequently this phenomenon occurs.

Golfer's swing leads to a spontaneous subcapsular liver haematoma.

We report the rare case of a patient presenting with a spontaneous hepatic subcapsular haematoma after playing golf. The patient had no underlying predisposing conditions. A CT scan of the abdomen/pelvis demonstrated a 1 cm deep low-attenuation subcapsular collection around the anterolateral aspect of the liver. The patient was treated conservatively and was discharged from inpatient care after 72 h. This is only the second reported case of a spontaneous subcapsular haematoma.

Detection of HTLV-I and -II in Scottish blood donor samples and archive donations.

BACKGROUND AND OBJECTIVES: Positive samples identified during routine serological screening for HCV (hepatitis C virus), HBV (hepatitis B virus) and HIV (human immunodeficiency virus) are confirmed by nucleic acid testing in the SNBTS (Scottish National Blood Transfusion Service) PCR Reference laboratory. Serological screening for HTLV-I (human T-cell lymphotropic virus type I) and -II was implemented in Scotland in November 2002, at which time a PCR assay was not available for confirmation. Our aim was to develop a real-time PCR assay that could be used for the confirmation of samples showing HTLV-I serological positive or indeterminate reactivity and to investigate whether a serologically silent carrier status exists ('Tax' only) in the Scottish donor population. MATERIALS AND METHODS: A real-time HTLV PCR was devised using a lymphoblastoid cell line which has HTLV-I sequence integrated in the genome (C8166 cells). These were spiked into peripheral blood mononuclear cells. The assay was evaluated on archived serologically confirmed HTLV-positive samples and new positives identified since implementation of screening. RESULTS: HTLV-I and -II were detected in cells and plasma from stored donations and a serological positive donation identified in routine screening. HTLV DNA can also be amplified from the plasma obtained from plasma preparation tubes. There was no evidence of a carrier status ('Tax' only) in 100 serologically negative blood donors tested. The PCR assay developed is reliable and sensitive, capable of identifying one copy of HTLV-I. CONCLUSIONS: The HTLV PCR is a useful addition for HTLV confirmation, especially in serologically indeterminate samples and for look-back studies. HTLV PCR confirmation will provide additional useful information for donor medical staff for counselling donors.

Acute hepatitis C virus seroconversion in a Scottish blood donor: HCV antigen is not comparable with HCV nucleic acid amplification technology screening.

BACKGROUND AND OBJECTIVES: This study was conducted to analyse the usefulness of hepatitis C virus (HCV) core antigen tests for the confirmation of HCV infection in a donor presenting as nucleic acid amplification technology (NAT) positive but negative for antibodies to HCV (anti-HCV). MATERIALS AND METHODS: Blood donations were screened, in parallel, for anti-HCV using the Abbott PRISM HCV Chemiluminescent immunoassay (ChLIA) and an 'in-house' HCV NAT (pools of up to 95 donations). An HCV NAT-positive antibody-negative donor was identified. Twelve follow-up samples were obtained and tested with various HCV antigen (including the recently marketed Trak-C second-generation assay) and HCV antibody assays. RESULTS: The single HCV NAT-positive, antibody-negative donation was identified from 1 117 681 donations screened in the 4-year period, July 1999 to June 2003. The index donation was positive by Ortho HCV core antigen enzyme immunoassay (EIA) and Ortho Trak-C (second-generation HCV core antigen EIA). An archive sample, taken 127 days prior to the index donation, was negative for all HCV markers. Subsequent samples demonstrated a loss of reactivity in the Ortho HCV core antigen EIA and reduced activity in the Ortho Trak-C until day 69. Immunoblot (Ortho RIBA-3) and HCV PRISM became positive on day 62, whilst Ortho HCV ELISA was not positive until day 132 or Biorad HCV ELISA until day 160. An alternative immunoblot (Innogenetics Innolia III) was positive from day 55. RNA levels fluctuated considerably during the follow-up period, being completely undetectable by routine screening methods at the time-point around seroconversion; subsequently, antibody was detected using all assays investigated. CONCLUSIONS: This HCV-converting blood donor provided a unique panel of samples for using to assess current (and future) HCV assay systems. The overall test results led to the conclusion that individual HCV antigen testing should not be considered as equivalent to HCV NAT minipool screening. Trak-C antigen testing may be considered as a suitable confirmatory assay for isolated HCV NAT reactivity.

The last glacial-Holocene transition in southern Chile.

Warming at the last glacial termination in the North Atlantic region was interrupted by a period of renewed glacial activity during the Younger Dryas chronozone (YDC). The underlying mechanism of this cooling remains elusive, but hypotheses turn on whether it was a global or a North Atlantic phenomenon. Chronological, sedimentological, and palaeoecological records from sediments of small lakes in oceanic southern Chile demonstrate that there was no YDC cooling in southern Chile. It is therefore likely that there was little or no cooling in southern Pacific surface waters and hence that YDC cooling in the North Atlantic was a regional, rather than global, phenomenon.

Physiological profile and predictors of cycling performance in ultra-endurance triathletes.

BACKGROUND: To report physiological profiles, and investigate the relationship between selected physiological variables and cycling performance in ultra-endurance triathletes. PARTICIPANTS: ten male (mean+/-SD, age; 32+/-5 years) ultra-endurance triathletes participated in the study. Physiological profiles were compared with 10 male age-matched control subjects. MEASURES: left ventricular structure (wall thickness [LVPWd], internal diameter [LVIDd], and mass [LVM]) and function (diastolic filling, fractional shortening, and stroke volume [SV]) were assessed using standard M-Mode, 2D, and Doppler echocardiography. Maximal and sub-maximal exercise gas exchange responses were measured on-line during a maximal ramping cycle-ergometer exercise test. RESULTS: Ultra-endurance triathletes demonstrated significantly larger LVPWd, LVIDd, LVM, SV, VO2max anaerobic threshold (AT), and power to body-mass ratio compared with controls. Cycling performance for both Ironman and half Ironman were significantly correlated with LVPWd, LVM, and SV. LVIDd was significantly correlated Ironman cycle time alone. Oxygen consumption (VO2) at AT, percentage of VO2max at AT, and peak power to bodymass ratio were significantly correlated to bike finish time in the half Ironman, but not Ironman. CONCLUSIONS: The correlation between cycling performance, LVM and SV suggests that the more conditioned athletes may be better able to maintain a high cardiac output during prolonged cycling. Sub-maximal gas exchange responses are predictors of cycling performance for the half-Ironman but not the Ironman. These results suggest that other factors including the longer duration swim prior to the cycling component, may impact upon cycle performance.

Cardiac fatigue following prolonged endurance exercise of differing distances.

PURPOSE: Recent echocardiographic studies have reported cardiac dysfunction following ultra-endurance exercise in trained individuals. The duration of exercise required to elicit cardiac dysfunction and the mechanisms underlying this phenomenon have not been fully elucidated. The aim of the present study was to examine the presence of cardiac dysfunction following a half-Ironman and Ironman triathlon in trained individuals. METHODS: 14 male triathletes (age: 32 +/- 5 yr; height: 180 +/- 8 cm; body mass: 75 +/- 9 kg) completed a half-Ironman triathlon. Following a 4-wk period, 10 of the original 14 triathletes completed an Ironman triathlon. All triathletes were assessed using ECG, echocardiography, and blood analysis pre-, immediately post-, and 48 h postrace for both distances. RESULTS: Echocardiographic results indicated diastolic and systolic left ventricular dysfunction, for both race distances, which were associated with altered relaxation characteristics and a reduced inotropic contractility, respectively. Following 48-h recovery, all echocardiographic measures were similar to resting values. Creatine kinase MB (CKMB) was significantly elevated immediately postrace for both distances; however, it accounted for less than 5% of the total CK value and in the presence of an elevated total CK and CKMM implied that the elevated CKMB was noncardiac in origin. Troponin-T, however, was significantly elevated immediately postrace for both distances and returned to normal following 48-h recovery indicating myocardial damage. CONCLUSIONS: Ironman and half-Ironman competition resulted in reversible abnormalities in resting left ventricular diastolic and systolic function. Results suggest that myocardial damage may be, in part, responsible for cardiac dysfunction, although the mechanisms responsible for this cardiac damage remain to be fully elucidated.

Clothing ventilation - update and applications.

The Environmental Ergonomics Unit at the P.O.W. provided a forum for the discussion and consolidation of ideas regarding the origins, current progress and the future development of the Clothing Ventilation Index. Crockford et al (1972) first developed the concept of clothing ventilation. The basic technique employs a trace gas dilution method for measuring the ventilation of the clothing microclimate. Ventilation is vital to the removal of sensible and insensible heat and, therefore, an important determinant of thermal comfort. Two techniques (Lotens and Havenith, 1986, 1988; Reischl et al, 1987) have subsequently been developed. The former method results in an average ventilation value for the total clothed-body surface area, whereas the latter method also takes into consideration regional changes in garment design as separate entities from the total ventilation, allowing for local modification in garment design. The Clothing Ventilation Index is a quantitative, relatively inexpensive, fast, reliable and repeatable technique. It can be used in context, in the working environment to predict the effectiveness, preference and suitability of garments and clothing assemblies; firstly, to ensure that protective clothing is worn and used correctly, and secondly, to improve performance by minimising heat strain, sweat retention and thermal discomfort. Further work on validating the techniques in terms of human responses to the thermal environment is required. Questions were also raised as to whether human beings or manikins should be used. The use of human beings in dynamic situations is of paramount importance; however, manikins could be used for purely physical measurements to test various assumptions in evaluating clothing ventilation. It is essential that body dimensions and posture are always specified. The seminar enabled researchers to identify with the proposed techniques, outline the advantages and importance of the Clothing Ventilation Index and focus future studies.